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Vibrational spectroscopy of protein structure often utilizes 13C18O-labeling of backbone carbonyls to further increase structural resolution. However, sidechains such as arginine, aspartate, and glutamate absorb within the same spectral region, complicating the analysis of isotope-labeled peaks. In this study, we report that the waiting time between pump and probe pulses in two-dimensional infrared spectroscopy can be used to suppress sidechain modes in favor of backbone amide I′ modes based on differences in vibrational lifetimes. Furthermore, differences in the lifetimes of 13C18O-amide I′ modes can aid in the assignment of secondary structure for labeled residues. Using model disordered and β-sheet peptides, it was determined that while β-sheets exhibit a longer lifetime than disordered structures, amide I′ modes in both secondary structures exhibit longer lifetimes than sidechain modes. Overall, this work demonstrates that collecting 2D IR data at delayed waiting times, based on differences in vibrational lifetime between modes, can be used to effectively suppress interfering sidechain modes and further identify secondary structures. [ABSTRACT FROM AUTHOR]

DNA replication stress (RS) is a widespread phenomenon in carcinogenesis, causing genomic instability and extensive chromatin alterations. DNA damage leads to activation of innate immune signaling, but little is known about transcriptional regulators mediating such signaling upon RS. Using a chemical screen, we identified protein arginine methyltransferase 5 (PRMT5) as a key mediator of RS-dependent induction of interferon-stimulated genes (ISGs). This response is also associated with reactivation of endogenous retroviruses (ERVs). Using quantitative mass spectrometry, we identify proteins with PRMT5-dependent symmetric dimethylarginine (SDMA) modification induced upon RS. Among these, we show that PRMT5 targets and modulates the activity of ZNF326, a zinc finger protein essential for ISG response. Our data demonstrate a role for PRMT5-mediated SDMA in the context of RS-induced transcriptional induction, affecting physiological homeostasis and cancer therapy.

Defects in tRNA biogenesis are associated with multiple neurological disorders, yet our understanding of these diseases has been hampered by an inability to determine tRNA expression in individual cell types within a complex tissue. Here, we developed a mouse model in which RNA polymerase III is conditionally epitope tagged in a Cre-dependent manner, allowing us to accurately profile tRNA expression in any cell type in vivo. We investigated tRNA expression in diverse nervous system cell types, revealing dramatic heterogeneity in the expression of tRNA genes between populations. We found that while maintenance of levels of tRNA isoacceptor families is critical for cellular homeostasis, neurons are differentially vulnerable to insults to distinct tRNA isoacceptor families. Cell-type-specific translatome analysis suggests that the balance between tRNA availability and codon demand may underlie such differential resilience. Our work provides a platform for investigating the complexities of mRNA translation and tRNA biology in the brain.

Orphan solute carrier (SLC) represents a group of membrane transporters whose exact functions and substrate specificities are not known. Elucidating the function and regulation of orphan SLC transporters is not only crucial for advancing our knowledge of cellular and molecular biology but can potentially lead to the development of new therapeutic strategies. Here, we provide evidence for the biological function of a ubiquitous orphan lysosomal SLC, the Major Facilitator Superfamily Domain-containing Protein 1 (MFSD1), which has remained phylogenetically unassigned. Targeted metabolomics revealed that dipeptides containing either lysine or arginine residues accumulate in lysosomes of cells lacking MFSD1. Whole-cell patch-clamp electrophysiological recordings of HEK293-cells expressing MFSD1 on the cell surface displayed transport affinities for positively charged dipeptides in the lower mM range, while dipeptides that carry a negative net charge were not transported. This was also true for single amino acids and tripeptides, which MFSD1 failed to transport. Our results identify MFSD1 as a highly selective lysosomal lysine/arginine/histidine-containing dipeptide exporter, which functions as a uniporter.

Traumatic brain injury (TBI) is an alteration of brain function caused by a sudden transmission of an external force to the head. The biomechanical impact induces acute and chronic metabolic changes that highly contribute to injury evolution and outcome. TBI heterogeneity calls for approaches allowing the mapping of regional molecular and metabolic changes underpinning disease progression, with mass spectrometry imaging (MSI) as an efficient tool to study the spatial distribution of small metabolites. In this study, we applied an innovative targeted atmospheric pressure-MALDI mass spectrometry imaging (AP-MALDI MSI) approach, starting from an extensive list of metabolites, representative of different metabolic pathways, individually validated on the tissue under analysis with original standards using 2,5-dihydroxybenzoic acid (DHB), to characterize the impact of TBI on regional changes to small metabolites in the brain. Brains from sham and TBI mice obtained 21 days post-injury were analyzed to examine the spatial metabolic profile of small metabolites belonging to different metabolic pathways. By a whole brain analysis, we identified four metabolites (alanine, lysine, histidine, and inosine) with higher abundance in TBI than sham mice. Within the TBI group, lysine, histidine, and inosine were higher in the hemisphere ipsilateral to the biomechanical impact vs. the contralateral one. Images showed a major involvement of the ipsilateral thalamus characterized by the increase of arginine, lysine, histidine, and inosine and a significant reduction of glutamic acid, and N-acetylaspartic acid compared to the contralateral thalamus. These findings indicate high-resolution imaging mass spectrometry as a powerful tool to identify region-specific changes after a TBI to understand the metabolic changes underlying brain injury evolution. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to investigate the impact of arginine on immune function and postoperative complications in colorectal cancer (CRC) patients. Methods: We conducted a comprehensive search to identify eligible RCTs in various databases, such as PubMed, Cochrane Library, EMBASE, Web of Science, MEDLINE, China National Knowledge Infrastructure (CNKI), Wanfang, VIP Medicine Information System (VIP), and Chinese Biomedical Database (CBM). This study aimed to examine IgA, IgG, and IgM levels as well as CD4+ and CD8+ counts as well as the CD4+/CD8+ ratio. Anastomotic leaking, length of stay (LOS), and surgical site infection (SSI) were included as secondary outcomes. Stata (StataCorp, version 14.0) was utilized for data analysis. To ensure the results were reliable, we used meta-regression, sensitivity analysis, and publication bias analysis. Results: A total of 24 publications (including 1883 patients) out of 681 that were retrieved fulfilled the inclusion criteria. The arginine group showed notable improvements in humoral immunity, with gains in IgA (SMD=0.45, 95% CI: 0.30-0.60), IgG (SMD=0.80, 95% CI: 0.64-0.96), and IgM (SMD=0.66, 95% CI: 0.39-0.93). With regards to cellular immunity, the arginine group exhibited a substantial increase in the CD4+ T cell count (SMD = 1.03, 95% CI: 0.67-1.38) compared to the control group. However, the CD4+/CD8+ ratio decreased significantly (SMD=1.37, 95% CI: 0.88-1.86) in the same arginine group, indicating a change in the balance between these two cell types. Additionally, the CD8+ T cell count showed a notable decrease (SMD=-0.70, 95% CI: -1.09 to -0.32) in the arginine group when compared to the control group. Anastomotic leakage was also considerably lower in the arginine group (SMD=-0.05, 95% CI: -0.08 to -0.02), the rate of SSIs was lower (RR = -0.02, 95% CI: -0.05-0), and the length of time patients spent in the hospital was shorter (SMD=-0.15, 95% CI: -0.38 to -0.08). Conclusions: After radiation treatment for CRC, arginine improves immune function and decreases the risk of infection problems. Trial registration: Registration with PROSPERO for this meta-analysis is number CRD42024520509. [ABSTRACT FROM AUTHOR]

Purpose: 68Ga-Trivehexin is an investigational PET radiopharmaceutical (NCT05799274) targeting αvβ6-integrin for PET imaging of carcinomas. 177Lu-D0301 is a structurally related therapeutic peptide tetramer. However, it showed considerable kidney uptake in rodents, impeding clinical applicability. We therefore evaluated the impact of different kidney protection strategies on the biodistribution of both agents in normal and tumor-bearing mice. Methods: Ex-vivo biodistribution of 68Ga-Trivehexin (90 min p.i.) and 177Lu-D0301 (90 min and 24 h p.i.) was determined in healthy C57BL/6N and H2009 (human lung adenocarcinoma) xenografted CB17-SCID mice without and with co-infusion of 100 µL of solutions containing 2.5% arginine + 2.5% lysine (Arg/Lys), 4% succinylated gelatin (gelofusine, gelo), or combinations thereof. Arg/Lys was injected either i.p. 30 min before and after the radiopharmaceutical, or i.v. 2 min before the radiopharmaceutical. Gelo was administered either i.v. 2 min prior activity, or pre-mixed and injected together with the radiopharmaceutical (n = 5 per group). C57BL/6N mice were furthermore imaged by PET (90 min p.i.) and SPECT (24 h p.i.). Results: Kidney uptake of 68Ga-Trivehexin in C57BL/6N mice was reduced by 15% (Arg/Lys i.p.), 25% (Arg/Lys i.v.), and 70% (gelo i.v.), 90 min p.i., relative to control. 177Lu-D0301 kidney uptake was reduced by 2% (Arg/Lys i.p.), 41% (Arg/Lys i.v.), 61% (gelo i.v.) and 66% (gelo + Arg/Lys i.v.) 24 h p.i., compared to control. Combination of Arg/Lys and gelo provided no substantial benefit. Gelo furthermore reduced kidney uptake of 177Lu-D0301 by 76% (90 min p.i.) and 85% (24 h p.i.) in H2009 bearing SCID mice. Since tumor uptake was not (90 min p.i.) or only slightly reduced (15%, 24 h p.i.), the tumor/kidney ratio was improved by factors of 3.3 (90 min p.i.) and 2.6 (24 h p.i.). Reduction of kidney uptake was demonstrated by SPECT, which also showed that the remaining activity was located in the cortex. Conclusions: The kidney uptake of both investigated radiopharmaceuticals was more efficiently reduced by gelofusine (61–85%) than Arg/Lys (25–41%). Gelofusine appears particularly suitable for reducing renal uptake of αvβ6-integrin targeted 177Lu-labeled peptide multimers because its application led to approximately three times higher tumor-to-kidney ratios. Since the incidence of severe adverse events (anaphylaxis) with succinylated gelatin products (reportedly 0.0062–0.038%) is comparable to that of gadolinium-based MRI or iodinated CT contrast agents (0.008% and 0.04%, respectively), clinical use of gelofusine during radioligand therapy appears feasible if similar risk management strategies as for contrast agents are applied. [ABSTRACT FROM AUTHOR]

Summary: In this study, we examined the physicochemical and functional properties of fava bean globulin fractions that are rich in legumin or vicilin proteins. The sulphur containing amino acids, branched chain amino acids, and arginine/lysine ratio obtained for legumin (1.89%, 18.32%, and 1.43%) are significantly (P < 0.05) higher than the 1.24%, 17.94%, and 1.05%, respectively, for the vicilin fraction. SDS‐PAGE results show that the legumin fraction had a wider range of polypeptide sizes (approximately 14–140 kDa) when compared to the approximately 12–68 kDa for vicilin. The surface hydrophobicity (So) of legumin (86.07) was significantly (P < 0.05) lower compared with vicilin (118.19). The legumin had higher protein solubility (approximately 40–50%) than the vicilin (0%) at pH 3 and 4, but vicilin solubility was higher at pH 6–8. The vicilin had higher (83.58%) in vitro protein digestibility than the legumin (78.24%). However, the legumin had higher oil‐holding capacity, lower least gelation concentration, and formed emulsions at pH 3, 7, and 9 with smaller mean oil droplet sizes than the vicilin. Foam formation was better with increased levels of α‐helix secondary structure. We conclude that pH of the environment was a stronger determinant of protein functionality than the sample protein concentration. [ABSTRACT FROM AUTHOR]

Ageing is a natural ontogenetic phenomenon that entails a decrease in the adaptive capacity of the organism, as a result of which the body becomes less adaptable to stressful conditions. Nitrate and nitrite enter the body from exogenous sources and from nitrification of ammonia nitrogen by intestinal microorganisms. This review considers the mechanisms of action of l -arginine, a known inducer of nitric oxide (NO) biosynthesis, and nitrates as supplements in the processes of ageing and aggravated stress states, in which mechanisms of individual physiological reactivity play an important role. This approach can be used as an element of individual therapy or prevention of premature ageing processes depending on the different levels of initial reactivity of the functional systems. A search was performed of the PubMed, Scopus, and Google Scholar databases (n = 181 articles) and the author's own research (n = 4) up to May 5, 2023. The review presents analyses of data on targeted treatment of NO generation by supplementation with l -arginine or nitrates, which is a promising means for prevention of hypoxic conditions frequently accompanying pathological processes in an ageing organism. The review clarifies the role of the individual state of physiological reactivity, using the example of individuals with a high predominance of cholinergic regulatory mechanisms who already have a significant reserve of adaptive capacity. In studies of the predominance of adrenergic influences, a poorly trained organism as well as an elderly organism correspond to low resistance, which is an additional factor of damage at increased energy expenditure. Conclusion It is suggested that the role of NO synthesis from supplementation of dietary nitrates and nitrites increases with age rather than from oxygen-dependent biosynthetic reactions from l -arginine supplementation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Energy‐saving and low‐carbon baking processes, as well as the need to determine the flavor‐forming mechanisms of baked dried tofu, are becoming increasingly necessary. The application of emerging catalytic infrared radiation (CIR) technology in baking of dried tofu is considered of high interest due to the low energy consumption and high baking efficiency compared to traditional baking methods. Hence, this study aimed to investigate the evolution of aroma compounds in baked dried tofu during the CIR baking process and reveal relevant relationships between physical qualities, potential flavor precursors and key volatile compounds. RESULTS: The results showed that the surface color of dried tofu gradually turned an appetizing golden yellow color during the rapid heating process, caused by the uniform infrared radiation from the radiant emitters. Meanwhile, the moisture of dried tofu experienced minimal reduction and the hardness of dried tofu gradually increased with the formation of crust on the surface. In addition, 49 volatile compounds were identified by headspace solid‐phase microextraction–gas chromatography–mass spectrometry and 13 substances – 1‐hexanol, 1‐octen‐3‐ol, 1‐pentanol, heptanal, nonanal, hexanal, (E,E)‐2,4‐decadienal, (E,Z)‐2,4‐decadienal, octanal, (E)‐2‐octenal, (E)‐2‐nonenal, 2‐heptanone and 2‐pentylfuran – were confirmed as key aroma compounds. Moreover, the amino acids aspartic acid, glutamic acid, isoleucine, lysine and arginine, and the fatty acids butyric, caprylic, capric, tridecanoic, stearic, oleic and linolenic were responsible for the unique flavor of CIR‐baked dried tofu. CONCLUSION: Consequently, the findings can provide a scientific basis for manufacturers to achieve precise quality control and large‐scale production of CIR‐baked dried tofu products. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Optimal balance between macro- and microcirculation in critically ill patients is crucial for ensuring optimal organ perfusion. Nitric oxide (NO) is a regulator of vascular hemostasis and tone. The availability of NO is controlled by asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the availability of the NO substrates arginine and homoarginine. We investigated the changes in plasma concentrations of ADMA, SDMA, arginine, and homoarginine days 1–5 of intensive care unit (ICU) admission and the association between the change in concentration days 1–3 and 30-day all-cause mortality. Methods: Single-center cohort study of adult critically ill patients from the ICU at Copenhagen University Hospital – North Zealand. ADMA, SDMA, arginine, and homoarginine (NO-biomarkers) were measured on days 1–5. Initially, we determined the changes in NO-biomarkers days 1–5 with linear mixed models, and subsequently how the changes in NO-biomarkers days 1–3 were associated with 30-day all-cause mortality. Post-hoc we analyzed the association between plasma concentration at admission and 30-day all-cause mortality. Results: In total 567 out of 577 patients had plasma samples from days 1–5. Plasma concentrations of ADMA and arginine increased from days 1–5. SDMA concentrations increased from days 1–2, followed by a decrease from days 2–5. Concentrations of homoarginine did not change from days 1–3 but slightly increased from days 3–5. In total 512 patients were alive 3 days after ICU admission. Among these patients, a daily twofold increase in ADMA concentration from days 1–3 was associated with decreased mortality in multivariate analysis (HR 0.45; 95% CI 0.21–0.98; p = 0.046). An increase in SDMA, arginine, or homoarginine was not associated with mortality. Post-hoc we found that a twofold increase in ADMA or SDMA concentrations at admission was associated with mortality (HR 1.78; 95% CI 1.24–2.57; p = 0.0025, and HR 1.41; 95% CI 1.05–1.90; p = 0.024, respectively). Conclusions: Increasing ADMA concentrations on days 1–3 are inversely associated with mortality, however not with the same strength as high ADMA or SDMA concentrations at admission. We suggest that admission concentrations are the focus of future research on ADMA and SDMA as predictors of mortality or potential therapeutical targets in ICU patients. [ABSTRACT FROM AUTHOR]

An electrophilic arginine mimetic, 2-chloroacetamidine (CAM), was deployed to enable trypsin-mediated proteolysis at cysteine residues and to enhance mass spectrometry-based proteomic detection of cysteine-containing peptides. Illustrating the value of the CAM-capping strategy, proteogenomic analysis using a two-stage false discovery rate (FDR) search revealed 450% enhanced coverage of missense variants, when compared to established workflows. [ABSTRACT FROM AUTHOR]

Despite the immune system's role in the detection and eradication of abnormal cells, cancer cells often evade elimination by exploitation of various immune escape mechanisms. Among these mechanisms is the ability of cancer cells to upregulate amino acid-metabolizing enzymes, or to induce these enzymes in tumor-infiltrating immunosuppressive cells. Amino acids are fundamental cellular nutrients required for a variety of physiological processes, and their inadequacy can severely impact immune cell function. Amino acid-derived metabolites can additionally dampen the anti-tumor immune response by means of their immunosuppressive activities, whilst some can also promote tumor growth directly. Based on their evident role in tumor immune escape, the amino acid-metabolizing enzymes glutaminase 1 (GLS1), arginase 1 (ARG1), inducible nitric oxide synthase (iNOS), indoleamine 2,3-dioxygenase 1 (IDO1), tryptophan 2,3-dioxygenase (TDO) and interleukin 4 induced 1 (IL4I1) each serve as a promising target for immunotherapeutic intervention. This review summarizes and discusses the involvement of these enzymes in cancer, their effect on the anti-tumor immune response and the recent progress made in the preclinical and clinical evaluation of inhibitors targeting these enzymes. [ABSTRACT FROM AUTHOR]

Inhibitors of the interaction between Neuropilin-1 (NRP-1) and Vascular Endothelial Growth Factor-A165 (VEGF-A165) hold significant promise as therapeutic and diagnostic agents directed against cancers overexpressing NRP-1. In our efforts in this field, a few series of strong and fairly stable peptide-like inhibitors of the general formula Lys(Har)1-Xaa2-Xaa3-Arg4 have been previously discovered. In the current work, we focused on Lys(Har)-Dap/Dab-Pro-Arg sequence. The aim was to examine whether replacing C-terminal Arg with its homologs and mimetics would yield more stable yet still potent inhibitors. Upon considering the results of modelling and other factors, ten novel analogues with Xaa4 = homoarginine (Har), 2-amino-4-guanidino-butyric acid (Agb), 2-amino-3-guanidino-propionic acid (Agp), citrulline (Cit), 4-aminomethyl-phenylalanine [Phe(4-CH2-NH2)] were designed, synthesized and evaluated. Two of the proposed modifications resulted in inhibitors with activity slightly lower [e.g. IC50 = 14.3 μM for Lys(Har)-Dab-Pro-Har and IC50 = 19.8 μM for Lys(Har)-Dab-Pro-Phe(4-CH2-NH2)] than the parent compounds [e.g. IC50 = 4.7 μM for Lys(Har)-Dab-Pro-Arg]. What was a surprise to us, the proteolytic stability depended more on position two of the sequence than on position four. The Dab2-analogues exhibited half-life times beyond 60 h. Our results build up the knowledge on the structural requirements that effective VEGF-A165/NRP-1 inhibitors should fulfil. [ABSTRACT FROM AUTHOR]

Amino acids and their salts are amine compounds with great potential for the chemical absorption of CO2 via the amine method. The CO2 absorption properties of various amino acids and their salts have been previously reported. However, the detailed reaction mechanism of CO2 with basic amino acids in aqueous solutions has not yet been clarified. In this study, we focused on arginine (Arg), which has the highest basicity among the standard amino acids, and its monohydrochloride (ArgCl) and sodium (NaArg) salts for the dissolution of CO2 in the aqueous solutions of Arg, ArgCl, and NaArg. CO2 was chemically dissolved in aqueous Arg and NaArg solutions but not in the aqueous ArgCl solution. One‐dimensional 1H and 13C and two‐dimensional 1H‐13C heteronuclear multiple bond correlation nuclear magnetic resonance spectroscopy indicated that the final products in the aqueous Arg and NaArg solutions were protonated Arg and HCO3−. HCO3− was formed from both CO2‐bonded Arg/Arg− and CO32− intermediates in the aqueous NaArg solution but only from the CO2‐bonded Arg/Arg− intermediate in the aqueous Arg solution. In addition to their high environmental and biological compatibility, Arg and NaArg exhibit high CO2 absorption capacity, demonstrating their potential for practical use as naturally derived CO2 chemical absorbents. [ABSTRACT FROM AUTHOR]

Background: Precursor B-cell acute lymphoblastic leukemia (B-ALL) is the most common cancers in children. Failure of induction chemotherapy is a major factor leading to relapse and death in children with B-ALL. Given the importance of altered metabolites in the carcinogenesis of pediatric B-ALL, studying the metabolic profile of children with B-ALL during induction chemotherapy and in different minimal residual disease (MRD) status may contribute to the management of pediatric B-ALL. Methods: We collected paired peripheral blood plasma samples from children with B-ALL at pre- and post-induction chemotherapy and analyzed the metabolomic profiling of these samples by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). Healthy children were included as controls. We selected metabolites that were depleted in pediatric B-ALL and analyzed the concentrations in pediatric B-ALL samples. In vitro, we study the effects of the selected metabolites on the viability of ALL cell lines and the sensitivity to conventional chemotherapeutic agents in ALL cell lines. Results: Forty-four metabolites were identified with different levels between groups. KEGG pathway enrichment analyses revealed that dysregulated linoleic acid (LA) metabolism and arginine (Arg) biosynthesis were closely associated with pediatric B-ALL. We confirmed that LA and Arg were decreased in pediatric B-ALL samples. The treatment of LA and Arg inhibited the viability of NALM-6 and RS4;11 cells in a dose-dependent manner, respectively. Moreover, Arg increased the sensitivity of B-ALL cells to L-asparaginase and daunorubicin. Conclusion: Arginine increases the sensitivity of B-ALL cells to the conventional chemotherapeutic drugs L-asparaginase and daunorubicin. This may represent a promising therapeutic approach. [ABSTRACT FROM AUTHOR]

Background: Arginine is a conditionally essential amino acid that is depleted in critically ill or surgical patients. In pediatric and adult patients, sepsis results in an arginine-deficient state, and the depletion of plasma arginine is associated with greater mortality. However, direct supplementation of arginine can result in the excessive production of nitric oxide (NO), which can contribute to the hypotension and macrovascular hypo-reactivity observed in septic shock. Pegylated arginine deiminase (ADI-PEG20, pegargiminase) reduces plasma arginine and generates citrulline that can be transported intracellularly to generate local arginine and NO, without resulting in hypotension, while maintaining microvascular patency. The objective of this study was to assess the efficacy of ADI-PEG20 with and without supplemental intravenous citrulline in mitigating hypovolemic shock, maintaining tissue levels of arginine, and reducing systemic inflammation in an endotoxemic pediatric pig model. Methods: Twenty 3-week-old crossbred piglets were implanted with jugular and carotid catheters as well as telemetry devices in the femoral artery to measure blood pressure, body temperature, heart rate, and respiration rate. The piglets were assigned to one of three treatments before undergoing a 5 h lipopolysaccharide (LPS) infusion protocol. Twenty-four hours before LPS infusion, control pigs (LPS; n=6) received saline, ADI-PEG20 pigs (n=7) received an injection of ADI-PEG20, and seven pigs (ADI-PEG20 + CIT pigs [n=7]) received ADI-PEG20 and 250 mg/kg citrulline intravenously. Pigs were monitored throughout LPS infusion and tissue was harvested at the end of the protocol. Results: Plasma arginine levels decreased and remained low in ADI-PEG20 + CIT and ADI-PEG20 pigs compared with LPS pigs but tissue arginine levels in the liver and kidney were similar across all treatments. Mean arterial pressure in all groups decreased from 90 mmHg to 60 mmHg within 1 h of LPS infusion but there were no significant differences between treatment groups. ADI-PEG20 and ADIPEG20 + CIT pigs had less CD45+ infiltrate in the liver and lung and lower levels of pro-inflammatory cytokines in the plasma. Conclusion: ADI-PEG20 and citrulline supplementation failed to ameliorate the hypotension associated with acute endotoxic sepsis in pigs but reduced systemic and local inflammation in the lung and liver. [ABSTRACT FROM AUTHOR]

As one of the major limiting environment factors in aquaculture, ammonia nitrogen brings severe threat to the growth and survival of aquatic animals, especially mollusk in benthic zones. However, the molecular mechanism underlying the toxic response and tolerance of mollusks to ammonia nitrogen remain unclear. In this study, transcriptome, metabolome and physiological indicators were combined to investigate the metabolic mechanism of adult razor clam (Sinonvacula constricta), which was exposed to -46mg/L ammonia nitrogen for 1 day (A1) and 10 days (A10). It was observed that compared with A1, the contents of free amino acids, including taurine (Tau), alanine (Ala) and arginine (Arg), the activities of immune-related enzymes acid phosphatase (ACP) and alkaline phosphatase (AKP), and antioxidation-related enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) in hepatopancreas, were significantly increased in A10, while the content of malondialdehyde (MDA) was significantly decreased (P < 0.05). Furthermore, the contents of glucose and pyruvate in hepatopancreas, foot and hemolymph urea nitrogen (HUN) were significantly changed (P < 0.05). Meantime, the comparative transcriptome analysis between A1 and A10 groups revealed the effects of ammonia stress on immune defense, antioxidant system and metabolic pathway. Likewise, metabolomic analysis showed that ammonia exposure interfered with amino acid metabolism, lipid metabolism and carbohydrate metabolism, with metabolism related-genes changed according to RNA-seq analysis. By comparing the metabolites and transcripts profiles of A10 and A1, the expression of some genes involved in detoxification and ammonia excretion was significantly changed. Combined with the changes in metabolites, we speculated that the convert endogenous ammonia to alanine, alanine-glucose cycle and urea synthesis might be adaptive strategies of the razor clam after ammonia stress. Collectively, the combination of physiological, transcriptome and metabolome will greatly contribute to the progressively understand the toxicity of ammonia exposure and the defense mechanism of razor clam against ammonia toxicity, and provide new sights on the potential molecular mechanisms of ammonia adaptive strategies in benthic mollusk. [ABSTRACT FROM AUTHOR]

Background: The prevalence of sarcopenia is increasing in worldwide with accelerated aging process. The high dietary protein intakes are associated with improved muscle mass and strength especially in Asian countries. However, there are few researches on amino acid levels or mechanism exploration. We conducted a case-control study to explore the amino acid metabolic characteristics and potential mechanism of elderly women with sarcopenia using targeted amino acid metabolomics approach combined with an analysis of dietary intake. Methods: For our case-control study, we recruited women (65–75 y) from a Shanghai community with 50 patients with sarcopenia and 50 healthy controls. The consensus updated by the Asian Working Group on Sarcopenia in 2019 was used to screening for sarcopenia and control groups. We collected fasting blood samples and evaluated dietary intake. We used the amino acid-targeted metabolomics by ultra performance liquid chromatography tandem mass spectrometry to identify metabolic differentials between the case and control groups and significantly enriched metabolic pathways. Results: The case (sarcopenia) group had a lower intake of energy, protein, and high-quality protein (P < 0.05) compared to the control (healthy) group. We identified four differential amino acids: arginine (P < 0.001) and cystine (P = 0.003) were lower, and taurine (P = 0.001) were higher in the case group. Conclusion: Low levels of arginine in elderly women are associated with a higher risk of sarcopenia. [ABSTRACT FROM AUTHOR]

Biotin and arginine play crucial roles in lipid metabolism and may offer promising interventions against obesity. This study examined the combined effect of magnesium biotinate (MgB) and inositol-stabilized arginine silicate complex (ASI) on obesity-related oxidative imbalance, inflammation, lipid metabolism and neuromodulation in rats on a high-fat diet (HFD). Forty rats were divided into five groups: (a) control: rats were fed a standard diet containing 12% of energy from fat; (b) HFD: rats were fed the HFD with 42% of energy from fat; (c) HFD + MgB: rats were fed the HFD and given 0.31 mg/kg body weight (BW) MgB, (d) HFD + ASI: rats were fed the HFD and were given 12.91 mg/kg BW ASI), and (e) HFD + MgB + ASI: rats were fed the HFD and given 0.31 mg/kg BW MgB and 12.91 mg/kg BW ASI). The combined administration of MgB and ASI reduced the levels of serum cholesterol, free fatty acid (FFA), and malondialdehyde (MDA), as well as liver inflammatory cytokines, sterol regulatory element-binding protein 1-c (SREBP-1c), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) proteins (P < 0.001) compared to HFD rats without supplementation. Moreover, this combination increased the activities of antioxidant enzymes (P < 0.05) and boosted the brain-derived neurotrophic factor (BDNF), serotonin, dopamine (P < 0.001), as well as liver insulin receptor substrate 1 (IRS-1) and peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < 0.001). These findings suggest that combining MgB and ASI could deter liver fat accumulation and enhance lipid metabolism in HFD-fed rats by modulating various metabolic pathways and neuromodulators related to energy metabolism. This combination demonstrates potential in addressing obesity and its related metabolic dysfunctions. [ABSTRACT FROM AUTHOR]

NVA1309 is a non-brain penetrant next-generation gabapentinoid shown to bind Cavα2δ at R243 within a triple Arginine motif forming the binding site for gabapentin and pregabalin. In this study we have compared the effects of NVA1309 with Mirogabalin, a gabapentinoid drug with higher affinity for the voltage-gated calcium channel subunit Cavα2δ-1 than pregabalin which is approved for post-herpetic neuralgia in Japan, Korea and Taiwan. Both NVA1309 and mirogabalin inhibit Cav2.2 currents in vitro and decrease Cav2.2 plasma membrane expression with higher efficacy than pregabalin. Mutagenesis of the classical binding residue arginine R243 and the newly identified binding residue lysine K615 reverse the effect of mirogabalin on Cav2.2 current, but not that of NVA1309. [ABSTRACT FROM AUTHOR]

Low temperatures during germination inhibit seed growth, lead to small and weak seedlings, and significantly reduce the wheat yield. Alleviating the adverse effects of low temperature on wheat seed germination is highly important for achieving high and stable wheat yields. In this study, Tongmai 6 (insensitive) and Zhengmai 113 (sensitive), which have different low-temperature sensitivities during germination were treated with low temperature during germination. The transcriptome, metabolome and physiological data revealed that low temperature decreased the germination rate, downregulated the expression of a large number of genes involved in regulating glycometabolism, and inhibited carbon, nitrogen (especially amino acids) and energy metabolism in the seeds. Arginine content increased at low temperature, and its increase in the low-temperature-tolerant variety was significantly greater than that in the sensitive variety. Arginine priming experiment showed that treatment with an appropriate concentration of arginine improved the seed germination rate. The conversion of starch to soluble sugar significantly increased under exogenous arginine conditions, the content of key metabolites in energy metabolism increased, and the utilization of ATP in the seeds increased. Taken together, arginine priming increased seed germination at low temperature by relieving inhibition of seed carbon and nitrogen metabolism and improving seed energy metabolism. [ABSTRACT FROM AUTHOR]

Adaptation to the shortage in free amino acids (AA) is mediated by 2 pathways, the integrated stress response (ISR) and the mechanistic target of rapamycin (mTOR). In response to reduced levels, primarily of leucine or arginine, mTOR in its complex 1 configuration (mTORC1) is suppressed leading to a decrease in translation initiation and elongation. The eIF2a kinase general control nonderepressible 2 (GCN2) is activated by uncharged tRNAs, leading to induction of the ISR in response to a broader range of AA shortage. ISR confers a reduced translation initiation, while promoting the selective synthesis of stress proteins, such as ATF4. To efficiently adapt to AA starvation, the 2 pathways are cross-regulated at multiple levels. Here we identified a new mechanism of ISR/ mTORC1 crosstalk that optimizes survival under AA starvation, when mTORC1 is forced to remain active. mTORC1 activation during acute AA shortage, augmented ATF4 expression in a GCN2-dependent manner. Under these conditions, enhanced GCN2 activity was not dependent on tRNA sensing, inferring a different activation mechanism. We identified a labile physical interaction between GCN2 and mTOR that results in a phosphorylation of GCN2 on serine 230 by mTOR, which promotes GCN2 activity. When examined under prolonged AA starvation, GCN2 phosphorylation by mTOR promoted survival. Our data unveils an adaptive mechanism to AA starvation, when mTORC1 evades inhibition. [ABSTRACT FROM AUTHOR]

Renilla luciferase catalyzes the oxidation of coelenterazine to coelenteramide and results in the emission of a photon of light. Although Renilla luciferase has various applications in biotechnology, its low thermal stability limits the development of its applications. Arginine is a well-known stabilizing amino acid that plays a key role in protein stabilization against inactivation. However, its impact on enzyme properties is unpredictable. This study investigates the impact of arginine on the kinetics and thermal stability of Renilla luciferase. The enzyme's performance was significantly enhanced in the presence of arginine, with catalytic efficiency increasing by 3.31-fold and 3.08-fold when exposed to 0.2 M and 0.3 M arginine, respectively. Additionally, arginine improved the thermal stability of Renilla luciferase. Molecular dynamics simulation showed that the addition of 0.2 M arginine reduced the binding of coelenteramide, the reaction product and an enzyme inhibitor, to the active site of the Renilla luciferase. Therefore, the release of the product was accelerated, and the affinity of Renilla luciferase for coelenterazine increased. Furthermore, Molecular dynamics studies indicated an increased network of water molecules surrounding Renilla luciferase in the presence of 0.2 M arginine. This network potentially enhances the hydrophobic effect on the protein structure, ultimately improving enzyme stability. The findings of this study hold promise for the development of commercial kits incorporating Renilla luciferase. [ABSTRACT FROM AUTHOR]

Background: Inflammation is the hallmark of critical illness and triggers the neuro-endocrine stress response and an oxidative stress. Acute inflammation is initially essential for patient's survival. However, ongoing or exaggerated inflammation, due to persistent organ dysfunction, immune dysfunction or poor inflammation resolution, is associated to subsequent hypermetabolism and hypercatabolism that severely impact short and long-term functional status, autonomy, as well as health-related costs. Modulation of inflammation is thus tempting, with the goal to improve the short- and long-term outcomes of critically ill patients. Findings: Inflammation can be modulated by nutritional strategies (including the timing of enteral nutrition initiation, the provision of some specific macronutrients or micronutrients, the use of probiotics) and metabolic treatments. The most interesting strategies seem to be n-3 polyunsaturated fatty acids, vitamin D, antioxidant micronutrients and propranolol, given their safety, their accessibility for clinical use, and their benefits in clinical studies in the specific context of critical care. However, the optimal doses, timing and route of administration are still unknown for most of them. Furthermore, their use in the recovery phase is not well studied and defined. Conclusion: The rationale to use strategies of inflammation modulation is obvious, based on critical illness pathophysiology and based on the increasingly described effects of some nutritional and pharmacological strategies. Regretfully, there isn't always substantial proof from clinical research regarding the positive impacts directly brought about by inflammation modulation. Some arguments come from studies performed in severe burn patients, but such results should be transposed to non-burn patients with caution. Further studies are needed to explore how the modulation of inflammation can improve the long-term outcomes after a critical illness. [ABSTRACT FROM AUTHOR]

Summary: The study inquired the influences of l‐arginine and l‐lysine on the physicochemical properties (including weight loss rate, water activity, texture, colour, lipid and protein oxidation, residual nitrite content and total volatile basic nitrogen (TVB‐N) content) of low‐sodium and low‐phosphate Cantonese sausage during the 1‐ and 7‐day storage. The results showed that the addition of l‐arginine or l‐lysine reduced the weight loss rate, TBARS content, carbonyl group content and residual nitrite level, slightly decreased water activity, and enhanced L*, a* and b* values. Compared to the control, 0.3% l‐arginine or l‐lysine declined hardness and chewiness, while 0.6% l‐arginine or l‐lysine elevated these two parameters. However, the addition of l‐arginine or l‐lysine also led to an increase in TVB‐N content. Overall, l‐arginine and l‐lysine improved the qualities of low‐sodium and low‐phosphate Cantonese sausage, which might be attractive to meat product manufacturers. [ABSTRACT FROM AUTHOR]

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum stability at N/P ≥ 40. The synthesized conjugates, with a diameter of <100 nm, formed nano-complexes with siRNA and exhibited a stable range of zeta potential values (13–18 mV at N/P = 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of a successful cellular internalization of siRNA. The peptides oleyl-(WRH)3 and oleyl-(WRH)4 showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)4 demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells. [ABSTRACT FROM AUTHOR]

This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Objective: In this study, dentine surface was analysed through Environmental‐scanning‐electron‐microscopy (ESEM) with energy‐dispersive‐X‐ray‐spectrometry (EDX) and Fourier‐transform‐infrared‐spectroscopy (FTIR) with attenuated total‐reflectance (ATR) to assess the morpho‐chemical changes and variations in mineralization degree after demineralizing treatment, after five toothpastes application (HA & Citrate toothpaste, Zinc‐HA toothpaste, Calcium Sodium Phosphosilicate toothpaste, Arginine & Calcium carbonate toothpaste, Colgate‐Triple‐Action, and Control toothpaste), after soaking in artificial saliva and after citric acid attack. Methods: Ca/P, Ca/N and P/N ratios were calculated from EDX atomic data to evaluate the mineralization degree of dentine surface. The IR calcium phosphate (CaP)/collagen and carbonate/collagen ratios has been evaluated to assess the remineralization changes in dentine; the carbonate/collagen IR ratio was calculated to identify the nucleation of B‐type‐carbonated apatite and calcium carbonate. Results: ESEM–EDX and ATR–FTIR showed residuals of toothpastes after the treatments in all cases, with a general increase in the mineralization degree after soaking in artificial saliva and a decrease after acid attack. Treatment with Arginine & Calcium carbonate toothpaste showed the highest Ca/P value after treatment (Ca/P 1.62) and acid attack (Ca/P 1.5) in confirmation, IR showed the highest amount of carbonate after treatment and soaking in artificial saliva. Arginine and calcium carbonate toothpaste and HA and citrate toothpaste remained to a higher extent on the dentine surface and revealed a higher remineralization activity. These formulations showed higher resistance to demineralization attack, as demonstrated by a higher ICaP/IAmide II intensity ratio than those obtained after EDTA treatment. Conclusions: Toothpastes that remained to a higher extent on dentine surface (arginine and calcium carbonate toothpaste in particular) were more able to promote remineralization. The formed calcium phosphate (CaPs) phase was intimately bound to dentine rather than a simple deposit. [ABSTRACT FROM AUTHOR]

To investigate the metabolomic mechanisms by which changes in cardiorespiratory fitness (CRF) levels affect metabolic syndrome (MetS) risk factors and to provide a theoretical basis for the improvement of body metabolism via CRF in people with MetS risk factors, a comparative blood metabolomics study of individuals with varying levels of CRF and varying degrees of risk factors for MetS was conducted. Methods: Ninety subjects between the ages of 40 and 45 were enrolled, and they were categorized into low-MetS (LM ≤ two items) and high MetS (HM > three items) groups, as well as low- and high-CRF (LC, HC) and LCLM, LCLM, LCHM, and HCHM groups. Plasma was taken from the early morning abdominal venous blood. LC-MS was conducted using untargeted metabolomics technology, and the data were statistically and graphically evaluated using SPSS26.0 and R language. Results: (1) There were eight common differential metabolites in the HC vs. LC group as follows: methionine (↓), γ-aminobutyric acid (↑), 2-oxoglutatic acid (↑), arginine (↑), serine (↑), cis-aconitic acid (↑), glutamine (↓), and valine (↓); the HM vs. LM group are contrast. (2) In the HCHM vs. LCLM group, trends were observed in 2-oxoglutatic acid (↑), arginine (↑), serine (↑), cis-aconitic acid (↑), glutamine (↓), and valine (↓). (3) CRF and MetS risk factors jointly affect biological metabolic pathways such as arginine biosynthesis, TCA cycle, cysteine and methionine metabolism, glycine, serine, and threonine metabolism, arginine and proline metabolism, and alanine, aspartate, and glutamate metabolism. Conclusion: The eight common differential metabolites can serve as potential biomarkers for distinguishing individuals with different CRF levels and varying degrees of MetS risk factors. Increasing CRF levels may potentially mitigate MetS risk factors, as higher CRF levels are associated with reduced MetS risk. [ABSTRACT FROM AUTHOR]

The present study reports on the development, adaptation, and optimization of a novel monoenzyme conductometric biosensor based on a recombinant arginine deiminase (ADI) for the determination of arginine in dietary supplements with a high accuracy of results. Aiming for the highly sensitive determination of arginine in real samples, we studied the effect of parameters of the working buffer solution (its pH, buffer capacity, ionic strength, temperature, and protein concentration) on the sensitivity of the biosensor to arginine. Thus, it was determined that the optimal buffer is a 5 mM phosphate buffer solution with pH 6.2, and the optimal temperature is 39.5 °C. The linear functioning range is 2.5–750 µM of L-arginine with a minimal limit of detection of 2 µM. The concentration of arginine in food additive samples was determined using the developed ADI-based biosensor. Based on the obtained results, the most effective method of biosensor analysis using the method of standard additions was chosen. It was also checked how the reproducibility of the biosensor changes during the analysis of pharmaceutical samples. The results of the determination of arginine in real samples using a conductometric biosensor based on ADI clearly correlated with the data obtained using the method of ion-exchange chromatography and enzymatic spectrophotometric analysis. We concluded that the developed biosensor would be effective for the accurate and selective determination of arginine in dietary supplements intended for the prevention and/or elimination of arginine deficiency. [ABSTRACT FROM AUTHOR]

Cryptocaryon irritans is a highly detrimental parasite in mariculture, causing significant economic losses to the aquaculture industry of Larimichthys crocea. In recent years, copper and copper alloy materials have been used to kill parasites. In this study, the effect of copper plates on the tomont period of C. irritans was explored. The findings indicated that copper plates effectively eradicated tomonts, resulting in a hatching rate of 0. The metabolomic analysis revealed that a total of 2,663 differentially expressed metabolites (1,032 up-regulated and 1,631 downregulated) were screened in the positive ion mode, and 2,199 differentially expressed metabolites (840 up-regulated and 1,359 down-regulated) were screened in the negative ion mode. L-arginine and L-aspartic acid could be used as potential biomarkers. Copper plate treatment affected 25 metabolic pathways in the tomont, most notably influencing histidine metabolism, retinol metabolism, the biosynthesis of phenylalanine, tyrosine, and tryptophan, as well as arginine and proline metabolism. It was shown that high concentrations of copper ions caused a certain degree of disruption to the metabolome of tomonts in C. irritans, thereby impacting their metabolic processes. Consequently, this disturbance ultimately leads to the rapid demise of tomonts upon exposure to copper plates. The metabolomic changes observed in this study elucidate the lethal impact of copper on C. irritans tomonts, providing valuable reference data for the prevention and control of C. irritans in aquaculture. [ABSTRACT FROM AUTHOR]

Background: Puerariamontana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) and Schisandra sphenanthera Rehder & E.H. Wilson are traditional edible and medicinal hepatoprotective botanical drugs. Studies have shown that the combination of two botanical drugs enhanced the effects of treating acute liver injury (ALI), but the synergistic effect and its action mechanisms remain unclear. This study aimed to investigate the synergistic effect and its mechanism of the combination of Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) (PM) and Schisandra sphenanthera Rehder & E.H. Wilson (SS) in the treatment of ALI. Methods: High performance liquid chromatography (HPLC) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of botanical hybrid preparation of PM-SS (BHP PM-SS) against ALIwere comprehensively evaluated by the CCl4 induced ALI micemodel. Afterwards, symptom-oriented network pharmacology, transcriptomics and metabolomics were applied to reveal the underlying mechanism of action. Finally, the key target genes were experimentally by RT-qPCR. Results: Chemical analysis and pharmacodynamic experiments revealed that BHP PM-SS was superior to the single botanical drug, especially at 2:3 ratio, with a better dissolution rate of active ingredients and synergistic anti-ALI effect. Integrated symptom-oriented network pharmacology combined with transcriptomics and metabolomics analyses showed that the active ingredients of BHP PM-SS could regulate Glutathione metabolism, Pyrimidine metabolism, Arginine biosynthesis and Amino acid sugar and nucleotide sugar metabolism, by acting on the targets of AKT1, TNF, EGFR, JUN, HSP90AA1 and STAT3, which could be responsible for the PI3K-AKT signaling pathway, MAPK signaling pathway and Pathway in cancer to against ALI. Conclusion: Our study has provided compelling evidence for the synergistic effect and its mechanism of the combination of BHP PM-SS, and has contributed to the development and utilization of BHP PM-SS dietary supplements. [ABSTRACT FROM AUTHOR]

A simple, solvent‐free arginine‐catalyzed aldol dimerization of levulinic acid was achieved via the simultaneous formation of a eutectic mixture. Dimers of levulinic acid are valued as biomass‐derived fine chemical precursors, with potential to upgrade to bio‐jet fuels or N‐containing functional chemicals. Typically, these dimers are produced as isomeric mixtures using high temperatures and a variety of solid inorganic catalysts or mineral acids. In this study, an organocatalytic and regioselective dimerization was achieved at 22 % conversion on either a bench or kilogram scale using mild temperatures and only L‐arginine as both a co‐solvent and catalyst. The intricate H‐bonding network comprising the eutectic solvent was harnessed to produce only one product, minimizing side reactivity and preserving the reactants for recycling. [ABSTRACT FROM AUTHOR]

In the fullerene cone HIV-1 capsid, the central channels of the hexameric and pentameric capsomers each contain a ring of arginine (Arg18) residues that perform essential roles in capsid assembly and function. In both the hexamer and pentamer, the Arg18 rings coordinate inositol hexakisphosphate, an assembly and stability factor for the capsid. Previously, it was shown that amino-acid substitutions of Arg18 can promote pentamer incorporation into capsid-like particles (CLPs) that spontaneously assemble in vitro under high-salt conditions. Here, we show that these Arg18 mutant CLPs contain a non-canonical pentamer conformation and distinct lattice characteristics that do not follow the fullerene geometry of retroviral capsids. The Arg18 mutant pentamers resemble the hexamer in intra-oligomeric contacts and form a unique tetramer-of-pentamers that allows for incorporation of an octahedral vertex with a cross-shaped opening in the hexagonal capsid lattice. Our findings highlight an unexpected degree of structural plasticity in HIV-1 capsid assembly. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests an association between maternal hypertension during pregnancy and mental health in the offspring. However, less is known about the role of hypertensive pregnancy in behavioral symptoms and brain structures of the offspring as well as in their developmental changes. Here, we utilized neuroimaging and behavioral data from 11,878 participants aged 9–10 years and their 2-year follow-up from the Adolescent Brain Cognitive Development (ABCD) study to investigate the long-term effects of maternal hypertension during pregnancy on early adolescent behavior and brain anatomy. Specifically, adolescents born of mothers with maternal hypertension are at risk of long-lasting behavioral problems, as manifested by higher externalizing and internalizing behavior scores at both 9–10 years and 11–12 years. These participants additionally presented with a higher cortical thickness, particularly in the fronto-parieto-temporal areas at 9–10 years. Four regions, including the left parahippocampus, left lateral orbitofrontal lobe, right superior temporal lobe and right temporal pole, remained thicker 2 years later. These findings were partially validated in rats modeled with Nω-nitro-L-arginine methyl ester (L-NAME) preeclampsia. Therefore, clinicians and women who experience hypertension during pregnancy should be warned of this risk, and healthcare providers should recommend appropriate clinical interventions for pregnancy-induced hypertension. [ABSTRACT FROM AUTHOR]

Introduction. The proline-rich decapeptide 10c (Bj-PRO-10c; ENWPHPQIPP) from the Bothrops jararaca snake modulates argininosuccinate synthetase (AsS) activity to stimulate L-arginine metabolite production and neuroprotection in the SH-SY5Y cell line. The relationships between structure, interactions with AsS, and neuroprotection are little known. We evaluated the neuroprotective effects of Bj-PRO-10c and three other PROs (Bn-PRO-10a, Bn-PRO-10c > Bn-PRO-10a-MK > Bn-PRO-10a. The structure of PROs and their correlations with enzyme activity revealed that histidine (H5) and glutamine (Q7) in Bj-PRO-10c potentiated their affinity for AsS. Conclusions. Our investigation provides the first insights into the structure and molecular interactions of PROs with AsS, which could possibly further their neuropharmacological applications. [ABSTRACT FROM AUTHOR]

Introduction: Osteoarthritis (OA) is a common degenerative disorder of the synovial joints and is usually an age-related disease that occurs due to continuous wear and tear of the cartilage in the joints. Presently, there is no proven medical management to halt the progression of the disease in the early stages. The purpose of our systematic review is to analyze the possible metabolites and metabolic pathways that are specifically involved in OA pathogenesis and early treatment of the disease. Materials and Methods: The articles were collected from PubMed, Cochrane, Google Scholar, Embase, and Scopus databases. "Knee", "Osteoarthritis", "Proteomics", "Lipidomics", "Metabolomics", "Metabolic Methods", and metabolic* were employed for finding the articles. Only original articles with human or animal OA models with healthy controls were included. Results: From the initial screening, a total of 458 articles were identified from the 5 research databases. From these, 297 articles were selected in the end for screening, of which 53 papers were selected for full-text screening. Finally, 50 articles were taken for the review based on body fluid: 6 urine studies, 15 plasma studies, 16 synovial fluid studies, 11 serum studies, 4 joint tissue studies, and 1 fecal study. Many metabolites were found to be elevated in OA. Some of these metabolites can be used to stage the OA Three pathways that were found to be commonly involved are the TCA cycle, the glycolytic pathway, and the lipid metabolism. Conclusion: All these studies showed a vast array of metabolites and metabolic pathways associated with OA. Metabolites like lysophospholipids, phospholipids, arginine, BCCA, and histidine were identified as potential biomarkers of OA but a definite association was not identified, Three pathways (glycolytic pathway, TCA cycle, and lipid metabolic pathways) have been found as highly significant in OA pathogenesis. These metabolic pathways could provide novel therapeutic targets for the prevention and progression of the disease. [ABSTRACT FROM AUTHOR]

Cation‐π interactions, often found in protein assemblies, are characterized by favorable electrostatic interactions between an aromatic π‐electron surface and a positively charged species. There are evidences that reveal the importance of cation‐π interactions between arginine and aromatic residues in protein structure and function. In this paper, the effect of cation‐π interactions on the aggregation propensity of peptides derived from human islet polypeptide (hIAPP) was explored using UV resonance Raman and fluorescence spectroscopy. By employing an analog of hIAPP22–29 in which Phe‐23 is replaced with tryptophan (NWGAILSS), we were able to demonstrate an increase in the amyloidogenic propensity of this mutant in the presence of Zn2+ that is attributable to cation‐π interactions. In contrast, no cation‐π interactions were observed when the cationic F23R analog of hIAPP22–29 (NRGAILSS) was allowed to interact with NWGAILSS. From these observations, it was surmised that in these peptides, the dominant interaction between arginine and tryptophan involves the π‐cloud of the guanidino group and the indole ring, not cation‐π interactions. The spectroscopic data, supported by density functional theory‐based simulation results, suggest that arginine‐tryptophan interaction involves π‐π stacking where the guanidino group is oriented parallel to the indole ring. These hydrophobic interactions, coupled with the hydrotropic effect of the guanidine functionality of arginine, led to a delay in the aggregation kinetics of NWGAILSS. These unique interactions were further exploited to design a peptide inhibitor of full‐length amylin self‐assembly. [ABSTRACT FROM AUTHOR]

Aquaporin‐2 (AQP2) is a member of the aquaporin water channel family. In the kidney, AQP2 is expressed in collecting duct principal cells where it facilitates water reabsorption in response to antidiuretic hormone (arginine vasopressin, AVP). AVP induces the redistribution of AQP2 from intracellular vesicles and its incorporation into the plasma membrane. The plasma membrane insertion of AQP2 represents the crucial step in AVP‐mediated water reabsorption. Dysregulation of the system preventing the AQP2 plasma membrane insertion causes diabetes insipidus (DI), a disease characterised by an impaired urine concentrating ability and polydipsia. There is no satisfactory treatment of DI available. This review discusses kinases that control the localisation of AQP2 and points out potential kinase‐directed targets for the treatment of DI. [ABSTRACT FROM AUTHOR]

Simple Summary: Arginine is an important amino acid for cattle, as it can help improve their immune response and the amount of fat in their meat. However, when arginine is given to cattle through their food, bacteria in their stomach can use it up before it has a chance to benefit the animal. In a recent study, researchers looked into whether adding a special protective coating to the arginine, using carnauba wax, could change the color, tenderness, and fat content of beef in three different breeds of heifers. We found that adding this protected arginine to the cattle's diet made the meat redder, more tender, and fattier after it was aged for 28 days. However, we also found that the breed of the cattle had a big impact on these qualities, with meat from Angus cattle being the most tender, even though it had slightly less fat compared to Hereford or Angus × Hereford crossbreeds. Hence, we concluded that both the protected arginine and the breed of the cattle can affect the quality of the beef. The objective of this exploratory study was to assess if microencapsulated arginine influences the physicochemical quality of beef. The study included three genetic groups: Angus, Hereford, and Angus × Hereford crossbreed. Two encapsulation systems were used with carnauba wax, at ratios of 3:1 and 2:1, carnauba wax:core (arginine), respectively. A control treatment was also included with no arginine addition. Encapsulated arginine with a 3:1 ratio increased redness by 19.66 at 28 d aged beef compared to the control and 2:1 ratio with values of 18.55 and 16.77, respectively (p = 0.01). Encapsulated arginine at a 3:1 ratio showed the lowest meat shear force values with 24.32 N at 28 d of ageing (p < 0.001). The Angus breed also had a low value of 24.02 N (p < 0.001). Finally, the highest values of intramuscular fat were observed with the inclusion of arginine in a 3:1 ratio. The fat value reached 2.12% with a 3:1 ratio (p = 0.002), while in the Angus breed it was 1.59%. The addition of carnauba wax-encapsulated arginine can improve meat quality. It enhances red color, tenderness, and marbling in bovine meat. [ABSTRACT FROM AUTHOR]

Protein cysteine S-glycosylation is a relatively rare and less well characterized post-translational modification (PTM). Creating reliable model proteins that carry this modification is challenging. The lack of available models or natural S-glycosylated proteins significantly hampers the development of mass-spectrometry-based (MS-based) methodologies for detecting protein cysteine S-glycosylation in real-world proteomic studies. There is also limited MS-sequencing data describing it as easier to create synthetic S-glycopeptides. Here, we present the results of an in-depth manual analysis of automatically annotated CID/HCD spectra for model S-glucopeptides. The CID spectra show a long series of y/b-fragment ions with retained S-glucosylation, regardless of the dominant m/z signals corresponding to neutral loss of 1,2-anhydroglucose from the precursor ions. In addition, the spectra show signals manifesting glucosyl transfer from the cysteine position onto lysine, arginine (Lys, Arg) side chains, and a peptide N-terminus. Other spectral evidence indicates that the N-glucosylated initial products of transfer are converted into N-fructosylated (i.e., glycated) structures due to Amadori rearrangement. We discuss the peculiar transfer of the glucose oxocarbenium ion (Glc+) to positively charged guanidinium residue (ArgH+) and propose a mechanism for the gas-phase Amadori rearrangement involving a 1,2-hydride ion shift. [ABSTRACT FROM AUTHOR]

Cystinuria is a genetic disorder, and in severe cases, it might lead to kidney failure. As an important biomarker for cystinuria, the level of arginine (Arg) in urine is a vital indicator for cystinuria screening. Therefore, it is urgently needed to detect Arg with high selectivity and sensitivity. In this work, a boric acid functionalized Zr-based metal–organic framework UiO-PhbA is prepared by grafting phenylboronic acid on UiO-66-NH2 through a Schiff base reaction using a covalent post-synthesis modification (CPSM) strategy. The prepared UiO-PhbA exhibits a sensitive and specific fluorescence "turn-on" response to Arg and can be exploited to detect Arg in human serum and urine samples with a broad linear range of 0.6–350 µM and low limit of detection (LOD) of 18.45 nM. This study provides a new and reliable rapid screening protocol for sulfite oxidase deficiency-related diseases. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the additional effects of perioperative immunonutrition (IMN) compared with preoperative immunonutrition (IMN) on anthropometric, nutritional, and biochemical parameters, hospital stay and postoperative complications in patients with colorectal cancer. Oral supplementation enriched with arginine, omega-3 fatty acids, and dietary nucleotides was given to 25 patients before and after the operation (Group 2); 25 patients received the same formula before surgery and standard isocaloric nutrition following the operation (Group 1). Postoperative body weight, body mass index (BMI), and middle upper arm circumference (MUAC) of Group 1 decreased more than Group 2 during follow-up (p < 0.05). The biochemical parameters, C-reactive protein (CRP), aspartate aminotransferase (AST) and fasting plasma glucose (FPG) were higher, and albumin was lower than the baseline in Group 1 compared to Group 2 (p < 0.05). There was a negative correlation between CRP and Nutrition Risk Screening (NRS) 2002 scores, and prealbumin and NRS 2002 scores had a positive correlation (p = 0.007, r = 0.384; p = 0.012, r = 0.352). There was no difference in hospital stay and postoperative complications between the groups (p > 0.05). Perioperative immunonutrition, compared to preoperative immunonutrition, can be used as a positive and effective approach in improving some anthropometric measurements and biochemical parameters in patients undergoing colorectal cancer surgery. [ABSTRACT FROM AUTHOR]

The reaction centre-light harvesting 1 (RC-LH1) core complex is indispensable for anoxygenic photosynthesis. In the purple bacterium Rhodobacter (Rba.) sphaeroides RC-LH1 is produced both as a monomer, in which 14 LH1 subunits form a C-shaped antenna around 1 RC, and as a dimer, where 28 LH1 subunits form an S-shaped antenna surrounding 2 RCs. Alongside the five RC and LH1 subunits, an additional polypeptide known as PufX provides an interface for dimerisation and also prevents LH1 ring closure, introducing a channel for quinone exchange that is essential for photoheterotrophic growth. Structures of Rba. sphaeroides RC-LH1 complexes revealed several new components; protein-Y, which helps to form the quinone channel; protein-Z, of unknown function and seemingly unique to dimers; and a tightly bound sulfoquinovosyl diacylglycerol (SQDG) lipid that interacts with two PufX arginine residues. This lipid lies at the dimer interface alongside weak density for a second molecule, previously proposed to be an ornithine lipid. In this work we have generated strains of Rba. sphaeroides lacking protein-Y, protein-Z, SQDG or ornithine lipids to assess the roles of these previously unknown components in the assembly and activity of RC-LH1. We show that whilst the removal of either protein-Y, protein-Z or ornithine lipids has only subtle effects, SQDG is essential for the formation of RC-LH1 dimers but its absence has no functional effect on the monomeric complex. [ABSTRACT FROM AUTHOR]

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Cancer is increasingly acknowledged as a metabolic disease, characterized by metabolic reprogramming as its hallmark. However, the precise mechanisms behind this phenomenon and the factors contributing to tumorigenicity are still poorly understood. In a recent publication in Cell, Mossmann and colleague reported a study unveiling arginine as a molecule with second messenger‐like properties that reshapes metabolism to facilitate the tumor development in hepatocellular carcinoma (HCC). Their research revealed that the RNA‐binding motif protein 39 (RBM39)‐mediated increase in asparagine synthesis results in increased arginine uptake. This establishes a positive feedback loop that sustains elevated levels of arginine and facilitates oncogenic metabolic reprogramming. Additionally, Mossmann et al. demonstrated that depleting RBM39 with indisulam effectively disrupts the proto‐oncogenic metabolic reprogramming in HCC. This discovery presents a novel treatment strategy for arginine‐dependent liver cancers. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a global health threat, necessitating innovative strategies for control and prevention. This comprehensive review explores the Mycobacterium tuberculosis Lysine Exporter (LysE) gene, unveiling its multifaceted roles and potential uses in controlling and preventing tuberculosis (TB). As a pivotal player in eliminating excess L-lysine and L-arginine, LysE contributes to the survival and virulence of M. tuberculosis. This review synthesizes findings from different electronic databases and includes 13 studies focused on the LysE of M. tuberculosis. The research unveils that LysE can be a potential drug target, a diagnostic marker for TB, and a promising candidate for vaccine development. The absence of LysE in the widely used BCG vaccine underscores its uniqueness and positions it as a novel area for TB prevention. In conclusion, this review underscores the significance of LysE in TB pathogenesis and its potential as a drug target, diagnostic marker, and vaccine candidate. The multifaceted nature of LysE positions it at the forefront of innovative approaches to combat TB, calling for sustained research efforts to harness its full potential in the global fight against this infectious disease. [ABSTRACT FROM AUTHOR]

This research evaluated two methods of arginine encapsulation, melt emulsification and nanoprecipitation, using a lipid matrix of carnauba wax and commercial polymers (Eudragit®) as a protective material. The ratios of wax–arginine were 1:1, 2:1, 3:1, and 4:1, while those of Eudragit® RS:RL were 30:70 and 40:60 in proportions of 1:0.5 and 1:1 Eudragit®–arginine. The microcapsules were morphostructurally characterized by scanning electron microscopy, and a microelement analysis was performed via energy-dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. Additionally, in vitro digestibility was used to determine the protection efficiency. Both encapsulated systems presented regular (crystals) and spherical (microcapsules) polyhedral morphologies. Qualitative nitrogen decreased significantly as the wax ratio increased in the wax–arginine formulations. The formulations with a 1:1 Eudragit:–arginine ratio (1000 mg arginine) produced a higher nitrogen content in the encapsulated systems than the formulations containing 500 mg of arginine. The 2:1 and 3:1 wax–arginine formulations had the lowest degradability after 5 h of rumen fluid exposure (40.7 and 21.26%, respectively) in comparison with 100% unencapsulated arginine. The 3:1 wax–arginine formulation is an efficient encapsulating system which protects against rumen degradation. The more intense absorption bands at 1738 cm−1 and 1468 cm−1 associated with the C=O and C-H groups in carnauba wax indicate that arginine was more protected than in the other systems. [ABSTRACT FROM AUTHOR]

Identifying genetic modifiers of familial amyotrophic lateral sclerosis (ALS) may reveal targets for therapeutic modulation with potential application to sporadic ALS. GGGGCC (G4C2) repeat expansions in the C9orf72 gene underlie the most common form of familial ALS, and generate toxic arginine-containing dipeptide repeats (DPRs), which interfere with membraneless organelles, such as the nucleolus. Here we considered senataxin (SETX), the genetic cause of ALS4, as a modifier of C9orf72 ALS, because SETX is a nuclear helicase that may regulate RNA-protein interactions involved in ALS dysfunction. After documenting that decreased SETX expression enhances arginine-containing DPR toxicity and C9orf72 repeat expansion toxicity in HEK293 cells and primary neurons, we generated SETX fly lines and evaluated the effect of SETX in flies expressing either (G4C2)58 repeats or glycine-arginine-50 [GR(50)] DPRs. We observed dramatic suppression of disease phenotypes in (G4C2)58 and GR(50) Drosophila models, and detected a striking relocalization of GR(50) out of the nucleolus in flies co-expressing SETX. Next-generation GR(1000) fly models, that show age-related motor deficits in climbing and movement assays, were similarly rescued with SETX co-expression. We noted that the physical interaction between SETX and arginine-containing DPRs is partially RNA-dependent. Finally, we directly assessed the nucleolus in cells expressing GR-DPRs, confirmed reduced mobility of proteins trafficking to the nucleolus upon GR-DPR expression, and found that SETX dosage modulated nucleolus liquidity in GR-DPR-expressing cells and motor neurons. These findings reveal a hitherto unknown connection between SETX function and cellular processes contributing to neuron demise in the most common form of familial ALS.